Anti-fibrotic, muscle-promoting antibody-drug conjugates for the improvement and treatment of DMD

Fibrosis, characterized by the deposition of excess and disorganized extracellular matrix (ECM), is a key pathological hallmark of multiple diseases, including Duchenne muscular dystrophy (DMD). Aiming to inhibit fibrosis progression, we generated an antibody-drug conjugate (ADC) that delivers an innovative small molecule conjugate to inhibit the ECM-modifying enzyme Lysyl oxidase (LOX) specifically in fibrotic lesions by targeting M2 macrophages. Administration of the ADC to <i>mdx</i> mice, the murine model of DMD, results in ADC accumulation in fibrotic muscles without affecting healthy tissues. Long-term ADC treatments of adult <i>mdx</i> mice lead to inhibition of the fibrotic process and to significant improvement of cardiac and skeletal muscle function. Our study demonstrates that targeted inhibition of LOX-dependent fibrotic diseases, such as DMD, facilitates improved outcomes for muscular dystrophies.